A Study of HER2+ Breast Cancer Patients With Active Brain Metastases Treated With Afatinib & T-DM1 vs. T-DM1 Alone

NCT04158947 | Unknown Phase 2

• 1 other identifier: HER2BAT
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 4

Brief Summary

This study is being done for the following reasons: The study has two parts. The purpose of the first part (Phase I) of the study is to find out the highest dose of Afatinib that can be given safely with T-DM1. The purpose of the second part of the study (Phase II) is to find out whether the dose of Afatinib with T-DM1 determined in Phase I will keep breast cancer from getting worse for a period of time.

Conditions

HER2-positive Breast Cancer; Brain Metastases

Keywords

HER2-positive Breast Cancer; Brain metastases; T-DM1; Afatinib

Outcome Measures

Primary Outcomes (2)

• Safety and tolerability of T-DM1 and Afatinib to determine the recommended Phase II dose (RP2D)

  If 1 of 3 patients in this cohort experiences a dose limiting toxicity (DLT), 3 more patients will be added at the same dose level. If 0 of 3 initial patients or 1 of 6 patients in an expanded cohort experiences a DLT, the dose for the next cohort will be escalated to dose level 2; otherwise, the combination will be considered too toxic.

  21 days

• Objective Response Rate(ORR)

  The sum of complete response (CR) rate and partial response (PR) rate by measurement of target lesions

  From the start of study therapy through study therapy stops, approximately 3 months

Secondary Outcomes (1)

• Progression-free Survival (PFS)

  From the start of study therapy through study therapy stops, approximately 3 months

Study Arms (2)

T-DM1 + Afatinib

EXPERIMENTAL

Trastuzumab emtansine (T-DM1) : 3.6 mg/kg IV Day 1 every 21 days. Afatinib: the highest dose of Afatinib with T-DM1 found in Phase I, po every day

Drug: Afatinib; Drug: T-DM1

T-DM1

ACTIVE COMPARATOR

Trastuzumab emtansine (T-DM1) :3.6 mg/kg IV Day 1 every 21 days.

Drug: T-DM1

Interventions

Afatinib DRUG

Dose-escalation Phase (Phase I) - Afatinib Dose-escalation will proceed on the basis of dose limiting toxicity (DLT) during Cycle 1 starting at 20 mg/day. Dose level 1: 20 mg/day; Dose level 2: 30 mg/day; Dose level 3: 40 mg/day; Dose level 4: 50 mg/day. Dose-evaluation Phase (Phase II) - Patients will receive the highest dose of Afatinib with T-DM1 found in Phase I as study therapy

Also known as: BIBW 2992

T-DM1 + Afatinib

T-DM1 DRUG

Dose-escalation Phase (Phase I) - Trastuzumab emtansine (T-DM1) will be given at 3.6 mg/kg IV Day 1 every 21 days. Dose-evaluation Phase (Phase II) - Trastuzumab emtansine (T-DM1) will be given at 3.6 mg/kg IV Day 1 every 21 days.

Also known as: Trastuzumab emtansine

T-DM1; T-DM1 + Afatinib

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients provided written informed consent
• Women aged 18-75 years old
• Histologically or cytologically confirmed HER2-positive (IHC 3+ or ISH+) breast cancer
• Patients with HER2 positive breast cancer with a documented central nervous system (CNS) recurrence/progression (by imaging) during or after a HER2 inhibitor (Trastuzumab and/or Lapatinib, Pyrotinib, Tucatinib) based therapy
• At least one measurable and progressive lesion in the CNS (≥10 mm on T1-weighted, gadolinium-enhanced MRI)
• Previous treatment with HER2 inhibitors to be discontinued prior to first study treatment administration (at least 14 days for trastuzumab and other antibodies, at least 7 days for lapatinib)
• Previous chemotherapy and hormonal therapy (adjuvant and metastatic regimens) allowed, but chemotherapy must have been discontinued at least 14 days and hormonal therapy at least 7 days prior to first study treatment administration
• Prior surgery, whole brain radiotherapy or stereotactic radiosurgery allowed provided that there is unequivocal evidence of one or more new and/or progressive brain metastases after completion of whole brain radiotherapy or stereotactic radiosurgery
• Previous radiotherapy allowed, but radiotherapy must have been discontinued at least 14 days prior to first study treatment administration
• Patients must have recovered to baseline condition or to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade = 1 from any acute CTCAE v. 5.0 grade =2 side effects of previous treatments
• Without infection of human immunodeficiency virus (HIV) on central laboratory assay results prior to randomization
• Alanine aminotransferase (ALT) \</= 2.5 × the upper limit of normal (ULN), Aspartate aminotransferase (AST) \</= 2.5 × ULN prior to randomization
• Total bilirubin (TBIL) \</= 1.25 × ULN
• Alkaline phosphatase (ALK) \</= 2.5 × ULN
• Gamma glutamyl transpeptidase (GGT) \</= 2.5 × ULN

You may not qualify if:

• Lack of histological or cytological confirmation of HER2-positive (IHC 3+ or ISH-positive) breast cancer
• Suffering cerebral hernia
• Only meningeal metastasis
• Earlier exposure to doxorubicin or pirarubicin at a dosage of more than 360 mg/m2
• Earlier exposure to epirubicin at a dosage of more than 900 mg/m2
• Prior treatment with HER2-tyrosine kinase inhibitor other than Lapatinib, Neratinib, Pyrotinib and Tucatinib, such as Afatinib, Erlotinib, Icotinib, Gefitinib and Osimertinib
• Treatment with trastuzumab emtansine within 6 months
• Any other current malignancy or malignancy diagnosed within the past five years (other than carcinoma in situ or stage Ia carcinoma of the cervix, skin basal cell carcinoma and papillary thyroid carcinoma at early stage)
• Active infection with human immunodeficiency virus (HIV) prior to first study treatment administration.
• History of participating any other clinical trials within 30 days prior to randomization
• Known hypersensitivity (Grade 3 or 4) to TDM1 or Afatinib or the excipients of any of the trial drugs
• Significant chronic or recent acute gastrointestinal disorders with diarrhoea as a major symptom e.g. Crohn's disease, malabsorption or Common Terminology Criteria (CTC) grade =2 diarrhoea of any aetiology
• Pregnancy or lactation
• Current severe systemic disease (for example, clinically significant cardiovascular, pulmonary, or renal disease)
• Legal incompetence or limitation.

Sponsors & Collaborators

• xuexin he: lead

Study Sites (4)

Peking University International Hospital

Beijing, Beijing Municipality, 102206, China

NOT YET RECRUITING

Sun Yat-sen University Cancer Center (SYSUCC)

Guangzhou, Guangdong, 510000, China

NOT YET RECRUITING

Kiang Wu Hospital

Macao, Macao, 820002, China

NOT YET RECRUITING

The Second Affiliated Hospital of Zhejiang University School of Medicine (SAHZU)

Hangzhou, Zhejiang, 310000, China

RECRUITING

MeSH Terms

Conditions

Brain Neoplasms

Interventions

Afatinib; Ado-Trastuzumab Emtansine

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Maytansine; Macrolides; Lactones; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Trastuzumab; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• xuexin he, MD

  The Second Affiliated Hospital of Zhejiang University School of Medicine (SAHZU)

  STUDY DIRECTOR

Central Study Contacts

xuexin he, MD

CONTACT

+86-18329139569; xuexinhe@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, Associate chief physician

Study Record Dates

• First Submitted: November 2, 2019
• First Posted: November 12, 2019
• Study Start: May 10, 2020
• Primary Completion: December 31, 2023
• Study Completion: March 31, 2024
• Last Updated: May 12, 2020

Record last verified: 2020-05

Locations

CN (4)